A phase 1 study of the OX40 agonist, BGB-A445, with or without tislelizumab, an anti-PD-1 monoclonal antibody, in patients with advanced solid tumors.
Authors: Jayesh Desai, Diwakar Davar, Sanjeev Deva, Bo Gao, Tianshu Liu, Marco Matos, Tarek Meniawy, Kenneth John O'Byrne, Meili Sun, Mark Voskoboynik, Kunyu Yang, Xinmin Yu, Xin Chen, Yan Dong, Hugh Giovinazzo, Shiangjiin Leaw, Deepa Patel, Tahmina Rahman, Yanjie Wu, Daphne Day
Journal: Journal of Clinical Oncology (2023)

2574 Background: OX40 is an immune costimulatory receptor, expressed on activated CD4 + and CD8 + T cells, which promotes T cell proliferation and survival in the tumor microenvironment. BGB-A445 is a novel monoclonal antibody (mAb) OX40 agonist that does not compete with endogenous OX40 ligand binding. BGB-A445 has demonstrated antitumor activity as a single agent and in combination with an anti-PD-1 mAb in preclinical studies. Here, we report data from the ongoing dose-escalation part of a multicenter, phase 1 dose escalation/expansion study (NCT04215978) of BGB-A445 alone or in combination with tislelizumab (TIS) in patients (pts) with advanced solid tumors. Methods: Eligible pts were enrolled into seven sequential dose escalation cohorts of BGB-A445 IV as monotherapy (Part A) or five increasing dose levels of BGB-A445 IV in combination with TIS 200 mg IV (Part B) on day 1 of 21-day cycles. Dose escalation was guided by a Bayesian (mTPI-2) approach. This study assessed safety, tolerability, pharmacokinetics (PK) profile, and preliminary antitumor activity (RECIST v1.1). Results: As of August 31, 2022, 59 pts were enrolled in Part A and 32 pts in Part B. Median (range) age was 59 years (28-80) and 61 years (37-75) in Parts A and B, respectively; 26 (44%) and 13 (41%) pts were male, respectively. ≥Grade 3 treatment-emergent AEs (TEAEs) were reported in 24 (41%) and 17 (53%) pts in Parts A and B, respectively; the most commonly reported (≥3 reported) ≥grade 3 TEAEs were gastrointestinal disorders (diarrhea, nausea, and abdominal pain). Serious TEAEs were reported in 23 (39%) pts in Part A and 16 (50%) in Part B. Treatment-related AEs leading to treatment discontinuation were reported in 1 (2%) pt in Part A and 0 (0%) pts in Part B. In Part A, all grade immune-mediated AEs (imAEs) were reported in 11 (19%) pts; no pts reported ≥grade 3 imAEs. In Part B, all grade imAEs were reported in 14 (44%) pts; ≥grade 3 imAEs were reported in 1 (3%) pt (one event each of rash maculopapular and diarrhea). There were no dose-limiting toxicities or concerning patterns of safety/tolerability observed. BGB-A445 PK (maximum concentration [C max ] and area under the curve from day 0 to 21 [AUC 0-21 ]) were linear and dose proportional in all tested dose ranges. In the efficacy-evaluable population of Parts A (n=50) and B (n=30), respectively, partial response was observed in 2 (4%) pts (unconfirmed) and 7 (23%) pts (confirmed); stable disease in 18 (36%) and 13 (43%) pts (confirmed), and progressive disease in 26 (52%) and 8 (27%) pts. Conclusions: In the dose escalation part of this study, BGB-A445 alone or in combination with TIS was generally well tolerated across all doses in pts with advanced solid tumors, and demonstrated preliminary antitumor activity as both a single and combination agent. The dose expansion part of the study is ongoing in pts with non-small cell lung cancer and head and neck squamous cell carcinoma. Clinical trial information: NCT04215978 .